Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the US causing serious adverse effects on women's reproductive health including complications of pregnancy, pelvic inflammatory disease, infertility, and cervical infections. The objectives of this project are to define the epidemiology, risk factors, transmission kinetics and pathogenesis of C. trachomatis infections in different population settings and different disease states using new molecular amplification assays. Using non-invasive samples with molecular amplification assays for C. trachomatis we documented high rates of infection in sexually active adolescents in diverse cultural settings in six countries. Prevalence rates of chlamydia ranged from 3.9% in rural villages in Zimbabwe and Uganda, 11.1% in St. Petersburg, Russia, 5.5% in Lima, Peru, 8.8% in Fuzhou, China, and 1.2% in Chennai, India. In STD clinics in Baltimore infection rates are 20% for men, 11.4% for women and as high as 14% for high school students. We have determined that in high school students, 25% of infected students get re-infected within one year. The documented high rates of chlamydia in these countries and in the US raises serious concerns about the resurgence of STDs that may reflect a rise in high-risk behavior which may subsequently lead to further HIV transmission. In an effort to increase detection of infection, we have used the internet to offer sampling for chlamydia for women at home using self-obtained vaginal swabs which are mailed to the laboratory. Prevalence has been 14.7% in young women age 15-19 yr using these self obtained samples. Future sampling of populations at home will include males, as well as screening for trichomonas. In a study of adolescent males in the US, we determined the cost effectiveness of chlamydia screening on admission to detention centers. Chlamydia prevalence in the population was 4.8% and the average number of female sexual partners per infected male was 1.6. We determined that universal screening by nucleic acid amplified test was the most cost- effective strategy preventing 37 more cases of pelvic inflammatory disease and three more cases of epididymitis than selective screening. With the implementation of universal screening we have compared self-administered vaginal swabs, cervical swabs, and first-catch urines for the diagnosis of chlamydial and gonorrhea infections in women from STD clinics in Baltimore. Results showed that a self-administered vaginal swab detected the most infections and was equivalent or better in sensitivity than cervical or urine samples. We have developed and evaluated real-time PCR assays for other STDs, such as Trichomonas vaginalis, Mycoplasma genitalium, and the LGV serovars of C. trachomatis. We have shown by multivariate analysis that both M. genitalium and T. vaginalis infections are associated with cervicitis in women and urethritis in men in addition to chlamydia and gonorrhea. Additionally we have participated in surgical and antibiotic treatment intervention studies in Ethiopia, Niger and Tanzania in efforts to control trachoma, the most common infectious cause of blindness worldwide. These studies have shown dramatic reductions in blindness in communities in which severe disease is first treated with surgery followed by community wide azithromycin mass therapy. In a randomized trial in Ethiopia, the combined surgical-azithromycin group had significantly fewer recurrences, 6.9/100 person-years compared with surgery-topical tetracycline 10.3/100 person-years (p = 0.04). There was no additional reduction in one arm that also treated household members compared with treating the surgical patients alone. Future studies will extend our efforts in noninvasive screening of chlamydia as a common STD and in the control of blinding trachoma.